Conventionally, for soft capsules, a shell composed mainly of gelatin and having a plasticizer such as glycerin added thereto has generally been employed. When an aqueous solution of a medicament or the like is filled in a capsule having such a water soluble polymer shell, the transition of water to the shell and swelling or dissolution of the shell due to this water cannot be avoided in the conventional technique. Soft capsules with such a shell are therefore not a product capable of enduring the distribution.
With a view toward filling soft capsules with a water soluble medicament or an aqueous extract of an animal or plant, various techniques have been investigated. For example, reported are a method of causing an aqueous solution of a medicament to adsorb to an excipient or the like, pulverizing it, suspending the powder in a lipophilic substance and then filling soft capsules with the suspension. Specifically the method comprises adding a surfactant to an aqueous solution of a medicament, uniformly mixing with a lipophilic component such as tocopherol acetate and then filling soft capsules with the resulting solution (Japanese Patent Application Laid-Open No. Sho 62-67020, Japanese Patent Application Laid-Open No. Hei 5-310566); a method of emulsifying a water-containing plant extract or the like in a fatty acid glyceride and then filling soft capsules with the resulting emulsion (Japanese Patent Laid-Open No. Sho 52-35178); a method of adding a water soluble polymer such as polyethylene glycol to an aqueous solution of a medicament such as pantethine and then filling the resulting highly viscous mixture to soft capsules (Japanese Patent Laid-Open No. Sho 56-30915); a method of forming soft capsules from a shell having a gelatin sheet and a polysaccharide sheet stacked one after another in order to impart the gelatin shell with water resistance (Japanese Patent Application Laid-Open No. Sho 63-164858), a method of forming capsules by using a shell made of gelatin and alginic acid, and dipping the resulting capsules in a calcium chloride solution to form an acid resistant film on the surface of the capsules (Japanese Patent Laid-Open No. Hei 1-313421), and a method of adding a large amount of edible fibers to the filling of capsules in order to keep its water content and filling the resulting paste in the capsules (Japanese Patent Laid-Open No. 2000-344661).
These capsules are however accompanied with the problem that lowering in the water activity of the capsule filling by adding, to an aqueous solution of the capsule filling, an oily substance, an O/W type emulsifying or suspending agent or a polymer substance to emulsify the aqueous solution or to heighten its viscosity deteriorates the properties, stability and platability of the medicament, or offers a hindrance to their production. In other words, a method of suspending a powdered medicament in a lipophilic substance or emulsifying or uniformly mixing the medicament in a water soluble polymer solution is not preferred, because it causes an rise in the production cost, limits an amount to be filled in a capsule, or sometimes damages the stability of the medicament by the heat applied during the pulverizing step, and moreover, impairs the original taste or smell of a medicament or extract which has placed an importance on its palatability or texture. The production of soft capsules made of stacked films involves such a problem that it requires special equipment in addition to an ordinarily employed rotary capsule filler. The method of filling capsules with a paste obtained by adding a large amount of edible fibers and saccharides to the filling also has such a defect that an inevitable stress on a feed pump during a capsule filling step becomes the cause of seizure.
Soft capsules having, encapsulated therein, a filling having a water activity of from 0.55 to 0.80 in a capsule shell having a water activity equal to or greater than the above-described value are developed, but problems such as softening of the capsule or adhesion between capsules occur when the capsule filling has a water activity of 0.80 or greater (Japanese Patent Application Laid-Open No. Sho 64-20078).
Accordingly, a demand continues to exist for capsules which can be retained stably even if encapsulated with a water soluble filling having a high water activity.
An object of the present invention is therefore to provide soft capsules which can be filled with an aqueous solution containing an active ingredient while retaining its high water activity without adding thereto an oily substance, O/W emulsifier, a water soluble polymer or the like.